The Barrett group works on medical genomics research at the Wellcome Trust Sanger Institute. We are interested in how genomic variation affects risk for diseases, and in finding ways to apply that knowledge to improve health care. We analyze both genome-wide association studies and next-generation sequence data collected on thousands of individuals, develop statistical and computational methods for these analyses, and pursue the integration of genomics with medicine.
We’re looking for talented PhD students and post-docs to join the team. If you’re interested, check out the information below, or contact Jeff directly.
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This year’s Biology of Genomes (BoG) meeting maintained its high standard with another display of excellent and exciting science. One of my favourite presentations was given by Matthew Stephens from the University of Chicago on the topic of False Discovery Rates (FDRs).
The FDR is a basic concept in statistical testing that we all come across in our research. By controlling the FDR, we aim to limit the expected proportion of false positives among significant loci identified by association studies. The idea is that under the null hypothesis (H0, that the locus is not associated with the trait), the observed p-values are expected to be distributed uniformly (Fig.1(a)); and under an alternative hypothesis (H1), more of the p-values should be close to zero (Fig.1(b)). In other words, the observed distributions of p-values in a genome-wide scan should be a mixture of these two distributions. The existing FDR methods find a maximum cutoff value (Fig. 1(c)) such that the results with smaller p-values are likely to be true positives from H1.
We’re currently advertising for two positions in the lab:
- A postdoc to work on genomic data analysis in inflammatory bowel disease, shared with Carl Anderson’s team
- A software developer to help build the tools the community needs for large-scale genomic analysis more generally, and to support the variety of projects happening in the team.
The first ad closes in just a few days, so apply soon if you’re interested (the second one is open for another couple of weeks).
Wendy offers a retrospective on the forward-looking atmosphere at last year’s American Society of Human Genetics meeting, in Boston
Looking into the future is something I felt the Annual ASHG conference focused on more this year than last year. One man who certainly has form for looking into the future is the Dermatologist Rudolf Happle. In the eighties Happle predicted a number of genetic conditions would be mosaic and, following the advent of whole exome sequencing, he has turned out to be correct in his predictions so far. Therefore I was rather pleased to catch him as the opening speaker in a stimulating session on mosaicism chaired by Leslie Besecker and William Dobyns.
One of my favorite presentations at ASHG this year was a poster given by Brendan Bulik-Sullivan from the Broad. Brendan and his colleagues attempted to answer a puzzling question which has come up quite often recently: “If we see an inflation of GWAS test statistics, is it because of polygenic risk (good) or population stratification (bad)?”
Recently I had my DNA genotyped by 23andMe. After working at Sanger for two years, I had been looking forward to finding out what my own genome had to say about myself, particularly regarding my ancestry. I am from Beijing and both of my parents are ethnically Han Chinese – the largest ethnic group which accounts for 92% population in China. Having witnessed my colleagues’ surprise at finding French, Ashkenazi and Scandinavian ancestry in their own DNA data, I could not help but get my hopes up to discover some surprising elements in my own ATGCs.
However, 23andMe left me feeling a little underwhelmed. Its ancestry analysis told me I’m 99.4% East Asian and Native American, a little like finding out that beef is 99.4% cow (something you can not always take from granted in the UK). Compared with the detailed breakdown you receive if you are European, such a vague composition is rather disappointing. Luckily, with a bit of experience in analysing genotype data, I could try other means. I combined my genotype with the east Asian cohort from our Inflammatory Bowel Disease (IBD) studies, and did a standard Principal Component Analysis (PCA) using WDIST, an experimental rewrite of the PLINK command-line tool which benefits from a vastly improved speed-up of the Identity-by-descent (—genome) calculation.
This is a guest post by Mari Niemi, an MSc student visiting the lab this year.
In the last few years, a major focus of the group has been identifying the genomic regions associated with risk of inflammatory bowel disease (IBD). Currently, there are 163 loci associated with the condition; the largest number of associations for a complex disease to date, explaining 13.6% Crohn’s disease and 7.5% ulcerative colitis total disease variance. These lists of associated loci are drawn up with some heavy-duty statistical computing, but still leave key questions about which genes in those regions are actually responsible for susceptibility to IBD – and what their role is in this complex plot? In order to understand more about the disease we need to functionally annotate these IBD candidate genes, and to do so we need to get our hands (quite literally) dirty in a laboratory!
On the weekend of 22nd of March, we went on our annual team retreat to Waterhouses, a village in the south of the Staffordshire Peak District. We set off from Oxford following a symposium at the Wellcome Trust Center of Human Genetics. Along the way we stopped in Lichfield to visit the famous Cathedral and the house of Erasmus Darwin (grandfather of Charles Darwin, www.erasmusdarwin.org). Surprisingly, Erasmus Darwin’s work hinted at the possibility of evolution, and although they had never met, Charles’ inspiration could have potentially come from his grandfather. We also had a nice meal in the Damn Fine Café, which had a selection of food and drink perfect for a cold winter’s afternoon.
We were really fortunate not to have lingered too long in Lichfield, as a large snowstorm rapidly descended upon the region. More »
One of the main research focuses of the Barrett group is to understand genetic associations with Inflammatory Bowel Disease (IBD), in particular with its two most common subtypes, Crohn’s disease and ulcerative colitis (UC).
Back in November 2012, in preparation for the ASHG meeting, I did a brief literature review on the development of IBD based on a number of selected publications. The motion chart below (created in R as used in the well-known Hans Rosling TED talk) shows an overview of the discovery of IBD disease loci since 2001, when three independent groups identified a CD risk gene on chromosome 16q12, NOD2, using linkage techniques.
Out today in Bioinformatics is an applications note describing our Olorin software. Olorin is an easy to use tool for filtering variants identified by high throughput family sequencing studies. Using Olorin, variants can be prioritized based on haplotype sharing across selected individuals in a pedigree as well as many other measures such as predicted functional consequence and population frequency.